Faculty Bibliography

Background/Purpose: Obesity is associated with poor response to treatment in patients with psoriatic arthritis (PsA), however, available data are mostly focused on tumor necrosis factor inhibitor (TNFi) initiators with only a few studies that have examined this association with initiators of other therapies. There are even fewer studies with patient reported outcome (PRO) measures as the outcomes of interest in PsA treatment. The clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) is a composite measure of disease activity in PsA and the, Routine Assessment of Patient Index Data 3 (RAPID3) and Psoriatic Arthritis Impact of Disease (PsAID) are PROs used in PsA. We examined the association of obesity with change in cDAPSA, RAPID3, PsAID among patients with PsA initiating TNFi, interleukin 17 inhibitors (IL17i) and oral small molecules (OSM).
Method(s): Patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the US between 2016-2020, initiated therapy with either TNFi, IL17i or OSM and completed at least one follow up visit. Treatment response was assessed by change in cDAPSA, RAPID3, or PsAID. Patients were stratified based on body mass index category (normal weight = BMI 19 to < 25 kg/m², overweight = BMI 25 to < 30 kg/m², obese = BMI >= 30 kg/m²). Baseline characteristics were reported descriptively. BMI category and its association with change in the outcomes of interest was examined in univariable and age-and-sex adjusted linear regression models.
Result(s): A total of 310 patients were included in the analysis. The mean age of patients was 52 and 56% were female. At baseline, the mean cDAPSA was 17.3 (SD 12.7), the mean PsAID was 3.6 (SD 2.2), the mean RAPID3 was 10.9 (SD 5.8). Baseline scores were overall similar when stratified by BMI category (Table 1). The mean change in cDAPSA was lowest among obese patients (-2.91 (SD 9.56) in normal BMI, -2.29 (SD 11.48) in overweight BMI, and -1.42 (SD 12.33) in obese BMI). The mean change in RAPID3 was lowest among obese patients (-1.53 (SD 4.50) in normal BMI, -1.69 (SD 4.47) in overweight BMI, and -0.26 (SD 5.46) in obese BMI). The mean change in PsAID was lowest among obese patients (-0.58 (SD 1.48) in normal weight BMI, -0.72 (SD 1.47) in overweight BMI, and -0.17 (SD 1.98) in obese BMI) (Figure 1). These differences were not statistically significant, potentially due to sample size. In unadjusted and age-and-sex adjusted analyses (Table 2), compared to the normal BMI category, obese patients had less improvement in cDAPSA, RAPID3 and PsAID. Similar numerical reduction in improvement was also found in the TNFi initiators although there was not a stepwise decrease in improvement with increasing BMI in IL17i nor OSM initiators.
Conclusion(s): The mean change in the selected outcome measures (cDAPSA, RAPID3, PsAID) was lowest among obese patients compared to the other BMI categories. Interestingly, this pattern was observed primarily among TNFi initiators as opposed to OSM or IL17i initiators (Figure Presented)

Psoriatic arthritis (PsA) is a complex inflammatory disease with heterogeneous clinical features, which complicates psoriasis in 30% of patients. There are no diagnostic criteria or tests available. Diagnosis is most commonly made by identifying inflammatory musculoskeletal features in joints, entheses or the spine in the presence of skin and/or nail psoriasis and in the usual absence of rheumatoid factor and anti-cyclic citrullinated peptide. The evolution of psoriasis to PsA may occur in stages, although the mechanisms are unclear. In many patients, there may be little or no relationship between severity of musculoskeletal inflammation and severity of skin or nail psoriasis. The reason for this disease heterogeneity may be explained by differences in genotype, especially in the HLA region. New targeted therapies for PsA have been approved with additional therapies in development. These developments have substantially improved both short-term and long-term outcomes including a reduction in musculoskeletal and skin manifestations and in radiographic damage. With efforts underway aimed at improving our understanding of the molecular basis for the heterogeneity of PsA, a personalized approach to treating PsA may become possible.

Background/UNASSIGNED:Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods/UNASSIGNED:For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings/UNASSIGNED:67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset. Interpretation/UNASSIGNED:Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2. Funding/UNASSIGNED:National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, and Bloomberg Philanthropies COVID-19 Response Initiative Grant.

OBJECTIVES/OBJECTIVE:Although oral methotrexate (MTX) remains the anchor drug for RA, up to 50% of patients do not achieve a clinically adequate outcome. Concomitantly, there is a lack of prognostic tools for treatment response prior to drug initiation. Here we study whether inter-individual differences in the human gut microbiome can aid in the prediction of MTX efficacy in new-onset RA (NORA). METHODS:16S rRNA gene and shotgun metagenomic sequencing were performed on the baseline gut microbiomes of drug-naïve, NORA patients (n=26). Results were validated in an additional independent cohort (n=21). To gain insight into potential microbial mechanisms, ex vivo experiments coupled with metabolomics analysis evaluated the association between microbiome-driven MTX depletion and clinical response. RESULTS:Our analysis revealed significant associations between the abundance of gut bacterial taxa and their genes with future clinical response, including orthologs related to purine and methotrexate metabolism. Machine learning techniques were applied to the metagenomic data, resulting in a microbiome-based model that predicts lack of response to MTX in an independent group of patients. Finally, MTX levels remaining after ex vivo incubation with distal gut samples from pre-treatment RA patients significantly correlated with the magnitude of future clinical response, suggesting a possible direct effect of the gut microbiome on MTX metabolism and treatment outcomes. CONCLUSIONS:Together, these results provide the first step towards predicting lack of response to oral MTX in NORA patients and support the value of the gut microbiome as a possible prognostic tool and as a potential target in RA therapeutics.

The coronavirus disease 2019 (COVID-19; caused by SARS-CoV-2) pandemic has affected the healthcare system on a global scale, and we utilized the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) 2020 annual meeting to examine how COVID-19 might affect patients with psoriatic disease (PsD) and the clinicians who care for them. Pressing issues and concerns identified included whether having psoriasis increased the risk of acquiring COVID-19, vaccine safety, and the acceptability of telehealth. The general message from rheumatologists, dermatologists, infectious disease specialists, and patient research partners was that data did not suggest that having PsD or its treatment significantly increased risk of infection or more severe disease course, and that the telehealth experience was a success overall.

BACKGROUND:Sacroiliitis is an inflammatory arthritis of the sacroiliac joints and is associated with inflammatory bowel disease (IBD). Yet, sacroiliitis often goes undiagnosed in IBD, and the clinical association between IBD disease activity and sacroiliitis is not well established. Patients with Crohn's disease (CD) often receive magnetic resonance enterography (MRE) to assess disease activity, affording clinicians the opportunity to evaluate for the presence of sacroiliitis. We aimed to identify the prevalence and disease characteristics associated with sacroiliitis in CD patients undergoing MRE. METHODS:All CD patients undergoing MRE for any indication between 2014 and 2018 at an IBD referral center were identified. The MREs were reviewed for the presence of sacroiliitis based on bone marrow edema (BME) and structural lesions. We analyzed demographics, IBD characteristics, clinical and endoscopic disease activity, and management between CD patients with and without sacroiliitis. RESULTS:Two hundred fifty-eight patients with CD underwent MRE during the study period. Overall, 17% of patients had MR evidence of sacroiliitis, of whom 73% demonstrated bone marrow edema. Female gender, back pain, and later age of CD diagnosis were associated with sacroiliitis (P = 0.05, P < 0.001, P = 0.04, respectively). Disease location and CD therapy were not associated with sacroiliitis on MRE. Clinical, endoscopic, and radiographic disease activity were not associated with sacroiliitis on MRE. CONCLUSION/CONCLUSIONS:Sacroiliitis is a common comorbid condition in CD. With limited clinical clues and disease characteristics to suggest sacroiliitis, physicians may utilize MRE to identify sacroiliitis, especially in CD patients with back pain.

OBJECTIVES:Physical function is a core outcome in PsA. We examined the construct validity and responsiveness of three commonly used instruments to assess physical function in PsA: HAQ disability index (HAQ-DI), MultiDimensional HAQ (MDHAQ) and the Patient-Reported Outcomes Measurement Information System (PROMIS®) Global-10. METHODS:Between 2016 and 2019, patients with PsA were enrolled in the Psoriatic Arthritis Research Consortium longitudinal cohort study in the USA. Correlations were calculated at baseline and among change scores using Spearman's correlation coefficient. Standardized response means were calculated. Agreement with the 20% improvement cut-off was used to determine the potential effect of using MDHAQ or the PROMIS Global-10 physical health (GPH) subscore in place of HAQ-DI when assessing the ACR20. RESULTS:A total of 274 patients were included in the analysis. The mean age of patients was 49 years and 51% were male. At baseline, the mean HAQ-DI was 0.6 (s.d. 0.6; range 0-3), the mean MDHAQ was 1.8 (s.d. 1.6; range 0-10) and the mean GPH T-score was 43.4 (s.d. 9.3; range 0-100). All three instruments were strongly correlated at baseline (rho 0.75-0.85). Change scores were moderately correlated (rho 0.42-0.71). Among therapy initiators, the mean change between two visits in HAQ-DI, MDHAQ and GPH was -0.1 (s.d. 0.4), -0.2 (s.d. 1.2) and 2.5 (s.d. 6.1), respectively. The standardized response means were 0.18, 0.16 and 0.41, respectively. CONCLUSION:The three instruments tested are not directly interchangeable but have overall similar levels of responsiveness.

Objective/UNASSIGNED:To investigate the humoral and cellular immune response to mRNA COVID-19 vaccines in patients with immune-mediated inflammatory diseases (IMIDs) on immunomodulatory treatment. Methods/UNASSIGNED:Established patients at NYU Langone Health with IMID (n=51) receiving the BNT162b2 mRNA vaccination were assessed at baseline and after second immunization. Healthy subjects served as controls (n=26). IgG antibody responses to the spike protein were analyzed for humoral response. Cellular immune response to SARS-CoV-2 was further analyzed using high-parameter spectral flow cytometry. A second independent, validation cohort of controls (n=182) and patients with IMID (n=31) from Erlangen, Germany were also analyzed for humoral immune response. Results/UNASSIGNED:Although healthy subjects (n=208) and IMID patients on biologic treatments (mostly on TNF blockers, n=37) demonstrate robust antibody responses (over 90%), those patients with IMID on background methotrexate (n=45) achieve an adequate response in only 62.2% of cases. Similarly, IMID patients do not demonstrate an increase in CD8+ T cell activation after vaccination. Conclusions/UNASSIGNED:In two independent cohorts of IMID patients, methotrexate, a widely used immunomodulator for the treatment of several IMIDs, adversely affected humoral and cellular immune response to COVID-19 mRNA vaccines. Although precise cut offs for immunogenicity that correlate with vaccine efficacy are yet to be established, our findings suggest that different strategies may need to be explored in patients with IMID taking methotrexate to increase the chances of immunization efficacy against SARS-CoV-2 as has been demonstrated for augmenting immunogenicity to other viral vaccines. KEY MESSAGES/UNASSIGNED:These results suggest that patients on methotrexate may need alternate vaccination strategies such as additional doses of vaccine, dose modification of methotrexate, or even a temporary discontinuation of this drug. Further studies will be required to explore the effect of these approaches on mRNA vaccine immunogenicity.

OBJECTIVE:To update guidance regarding the management of psoriatic disease during the COVID-19 pandemic. STUDY DESIGN/METHODS:The task force (TF) includes 18 physician voting members with expertise in dermatology, rheumatology, epidemiology, infectious diseases, and critical care. The TF was supplemented by nonvoting members, which included fellows and National Psoriasis Foundation staff. Clinical questions relevant to the psoriatic disease community were informed by inquiries received by the National Psoriasis Foundation. A Delphi process was conducted. RESULTS:The TF updated evidence for the original 22 statements and added 5 new recommendations. The average of the votes was within the category of agreement for all statements, 13 with high consensus and 14 with moderate consensus. LIMITATIONS/CONCLUSIONS:The evidence behind many guidance statements is variable in quality and/or quantity. CONCLUSIONS:These statements provide guidance for the treatment of patients with psoriatic disease on topics including how the disease and its treatments affect COVID-19 risk, how medical care can be optimized during the pandemic, what patients should do to lower their risk of getting infected with severe acute respiratory syndrome coronavirus 2 (including novel vaccination), and what they should do if they develop COVID-19. The guidance is a living document that is continuously updated by the TF as data emerge.